Atopic Dermatitis Xử trí

Principles of therapy

Goals of Therapy  

The goals of therapy in atopic dermatitis are to reduce symptoms, achieve clear or almost clear skin, prevent exacerbations, and maintain long-term remission. Other goals would be a 75% improvement in severity scores, improved quality of life, minimized therapeutic risks, and avoidance of drug-related toxicities.  

Topical Therapy  

Fingertip unit rule (FTU), which is the amount of ointment expressed from a tube with a 5-mm nozzle and measured from the distal skin crease to the tip of the index finger and measuring about 0.5 gram, should be followed in applying topicals including anti-inflammatory agents. It covers approximately 2% of an adult body surface area.  

Atopic Dermatitis_Management 1

Pharmacological therapy

Topical Corticosteroids

Topical corticosteroids are used as first-line treatment for mild to severe atopic dermatitis and when non-pharmacological interventions have been unsuccessful. They provide rapid symptomatic relief for acute flare-ups and are also used for the prevention of relapses.

The choice of product will depend on the severity of the flare-up, distribution and site of the lesions, patient’s age and preference, and other factors like humidity.

They provide anti-inflammatory and antipruritic activity through several mechanisms. They induce alterations in leukocyte number and activity, suppress mediator release (histamine, prostaglandins), and promote enhanced response to agents that increase cyclic adenosine monophosphate (prostaglandin E₂ and histamine via the histamine-2 receptor).

Recommended restrictions should be followed regarding the intensity and duration of use especially in children on delicate skin areas (eg face, neck, and skin folds). Intermittent use (1 to 2 times per week) in combination with moisturizers is historically the standard therapy for atopic dermatitis. Continuous use can lead to adverse effects.

Topical corticosteroids are available in different potencies from mildly potent to very potent. Potency is also affected by the vehicle the product is formulated in (eg ointment, cream, and lotion in decreasing order of efficacy). The potency of topical corticosteroids does not relate to the percentage stated (eg Hydrocortisone 2.5% versus Betamethasone dipropionate 0.05%). The least potent but effective product should be used, especially if for long-term use. Mid- and high-potency preparations may be used (except when lesions are on the face, groin, or axillae) to control acute flares and then follow with lower potency preparations after clinical improvement is seen. Rebound flaring can occur if higher potency preparations are discontinued abruptly. A gradual decrease in potency should follow the use of higher potency preparations. Therapy-resistant lesions may require potent topical corticosteroids used under occlusion. 

Solutions  

Solutions are useful for the scalp or other hirsute areas. The alcohol content may be irritating when used on inflamed lesions.  

Lotions  

Lotions are useful for minimal application to a large area or on hirsute areas. They may also be used on exudative lesions and in hairy areas.  

Creams  

Creams are usually preferred for moist or weeping lesions. They may be preferred during periods of excessive heat or humidity. They are easier to apply but may be less effective.  

Ointments  

Ointments are generally used for dry, scaly, or lichenified lesions or if a more occlusive effect is needed (most occlusive vehicle). There are usually lesser additives used in ointments. Evaporative losses are also decreased.

Systemic Corticosteroids¹  

Short-term treatment (up to 1 week) with systemic corticosteroids should only be considered in treatment-resistant atopic dermatitis, acute severe exacerbations, and as a bridge therapy to other steroid-sparing systemic treatments. The recommended dose is 0.5 mg/kg body weight.  

They improve lesions but rebound flare-up usually occurs upon discontinuation. They should be used only for the short term. To decrease the chance of rebound effect, taper the oral form slowly while increasing topical corticosteroid treatment and continuously hydrating the skin.  

¹Various oral corticosteroids are available. Please see the latest MIMS for specific formulations and prescribing information. 

Calcineurin Inhibitors - Topical Immunomodulators

Steroid-sparing agents for acute and maintenance therapy, topical calcineurin inhibitors inhibit inflammatory cytokine transcription in activated T cells and other inflammatory cells through the inhibition of calcineurin.  

They are considered second-line therapy for moderate to severe atopic dermatitis. They are considered first-line treatment over topical corticosteroids when atopic dermatitis is unresponsive to steroid therapy, when atrophy or telangiectasia is present secondary to steroid use, when affected areas are either the face, anogenital area, and/or skin folds, and for long-term treatments. They are also used in patients with inadequate response or contraindication to other topical therapeutic agents.  

They may be used on all body locations for extended periods of time, especially the face, hands, and feet. There is no evidence of a causal link between the use of calcineurin inhibitors and cancers. 

Pimecrolimus  

The safety and efficacy of Pimecrolimus have been shown in children >2 years of age and adults with mild-moderate atopic dermatitis. Pruritus relief has been seen as early as day 3 of use and it does not cause atrophy. It prevents flare-ups and results in significant steroid-sparing effect when used for up to 12 months. When used in the early stages of the disease, it has been shown to be therapeutically advantageous over typical moisturizers plus topical corticosteroids with long-term use. 

Tacrolimus  

Tacrolimus is recommended for moderate to severe atopic dermatitis. It rapidly decreases the signs and symptoms of atopic dermatitis in adults and children >2 years of age. Improvement is seen within 3 to 7 days of therapy and sustained for at least 12 months. It is well-tolerated with transient skin burning or irritation and has less incidence of atrophy compared to steroids.  

Studies have confirmed the efficacy of Tacrolimus 0.03% compared to low-potency topical corticosteroids in children and the efficacy of Tacrolimus 0.1% compared to mid-potency topical corticosteroids in adults. 

Phosphodiesterase Type-4 (PDE-4) Inhibitors

Apremilast  

Apremilast may be considered in patients with moderate to severe atopic dermatitis unresponsive to standard treatments, but further studies are needed to establish its efficacy and safety.    

Crisaborole  

Crisabarole may be considered for mild to moderate atopic dermatitis in patients ≥3 months old. Studies showed improvement in symptoms (ie erythema, induration, oozing) with Crisaborole use. 

Immunosuppressants²  

Abrocitinib  

Abrocitinib is an oral Janus kinase (JAK) 1 inhibitor used for the treatment of refractory moderate to severe atopic dermatitis which is inadequately controlled with other systemic drugs (including biologics) or when the use of those therapies is not advisable. It may be used with or without topical corticosteroids. It is not recommended to be used in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.  

A large, randomized, safety clinical trial showed an increased risk of malignancy (lymphoma and lung cancer), all-cause mortality (including sudden cardiovascular death), major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke), and thrombosis (including pulmonary embolism and venous and arterial thrombosis) with another JAK inhibitor compared to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis.

Azathioprine  

Azathioprine is used for severe or refractory disease unresponsive or with contraindications to Ciclosporin therapy and most children respond to low doses. There is increasing evidence supporting its efficacy in severe refractory atopic dermatitis.  

It may cause nausea, fatigue, myalgia, liver dysfunction, and bone marrow depression in patients deficient in thiopurine methyltransferase (TPMT). TPMT levels should be monitored while the patient is on Azathioprine to test for myelosuppression.

Baricitinib  

Baricitinib is an oral selective JAK1 and JAK2 inhibitor which blocks signals of immune response and inflammation. It may be given as an option for treatment of moderate to severe atopic dermatitis in adults who are unresponsive or contraindicated to at least one systemic immunosuppressant (eg Ciclosporin, Methotrexate, Azathioprine, Mycophenolate mofetil). It may be an alternative to Dupilumab with the best supportive care and may be offered with topical corticosteroids.  

Studies showed Baricitinib, with or without corticosteroids, can reduce the severity and symptoms of atopic dermatitis compared with a placebo.    

It is important to assess patients after 8 weeks of treatment if there is an adequate response. An adequate response is defined as a reduction of at least 50% in EASI-50 score and at least 4 points in DLQI from the start of the treatment. 

Ciclosporin (Cyclosporin A)  

Ciclosporin is a first-line option for short-term use in chronic, severe refractory disease in adults who require systemic immunosuppressive treatment. The condition tends to return after discontinuation of therapy but not always at the original severity level.  

It may be used in children and adolescents with refractory or severe disease. Long-term use is not justified because of the risks of hypertension and renal and liver dysfunction. Combination therapy with UV light (eg UVA, UVB, PUVA) is not recommended due to the increased risk of skin cancer. 

Methotrexate  

Methotrexate may be considered for severe or refractory disease unresponsive or with contraindications to Ciclosporin therapy. Studies showed that the efficacy of Methotrexate for atopic dermatitis is comparable to that of Azathioprine and Ciclosporin. 

Mycophenolate mofetil  

Mycophenolate mofetil may be considered for severe or refractory disease unresponsive or with contraindications to Ciclosporin therapy.  

Ruxolitinib  

Topical Ruxolitinib is a selective JAK1 and JAK2 inhibitor that is approved by the United States Food and Drug Administration (US FDA) for short-term therapy of mild to moderate atopic dermatitis in immunocompetent patients ≥12 years old whose disease is not controlled with other topical therapies. 

Upadacitinib  

Upadacitinib is an oral selective and reversible inhibitor of JAK enzymes (preferentially JAK1 or JAK1/3), which are intracellular enzymes involved in the stimulation of hematopoiesis and immune cell function through a signaling pathway.  

It is used in patients ≥12 years old with refractory moderate to severe atopic dermatitis which is inadequately controlled with other systemic drugs (including biologics) or when the use of those therapies is not advisable.  

It is not recommended to be used in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.  

A large, randomized, safety clinical trial showed an increased risk of malignancy (lymphoma and lung cancer), all-cause mortality (including sudden cardiovascular death), MACE (defined as cardiovascular death, myocardial infarction, and stroke), and thrombosis (including pulmonary embolism and venous and arterial thrombosis) with another JAK inhibitor compared to TNF inhibitors in patients with rheumatoid arthritis.  

²Various immunosuppressants are available. Please see the latest MIMS for specific formulations and prescribing information.

Biologic Therapy

Dupilumab  

Dupilumab is a human immunoglobulin (Ig) G4 monoclonal antibody approved for use in patients ≥12 years of age with moderate to severe atopic dermatitis uncontrolled by first-line treatments and who are candidates for systemic therapy. It binds to the interleukin-4Ra (IL-4Ra) subunit thereby inhibiting IL-4 and IL-13 cytokine-induced responses which include proinflammatory cytokine, chemokines, and IgE release. Combination with emollients and as-needed topical anti-inflammatory agents are recommended.  

Tralokinumab  

Tralokinumab is recommended for adult patients with moderate to severe atopic dermatitis uncontrolled by topical therapies and are candidates for systemic therapy. It is a human, high-affinity IgG4 monoclonal antibody which acts by neutralizing IL-13. Combination treatment with topical corticosteroids, topical calcineurin inhibitors, and UV light is possible. 

Other Biologicals  

Further studies are needed to prove the efficacy of Nemolizumab, Rituximab, Mepolizumab, Omalizumab, and Ustekinumab for atopic dermatitis. Trial treatment with Mepolizumab may be considered in select patients unresponsive to standard therapies. Lebrikizumab, Nemolizumab, Tralokinumab, and Tezepelumab are being studied for atopic dermatitis.

Retinoid

Alitretinoin is a derivative of Isotretinoin with anti-inflammatory effects used for severe chronic hand atopic dermatitis unresponsive to first-line treatments. Concomitant treatment with topical corticosteroids, topical calcineurin inhibitors, and emollients is possible. 

Allergen-specific Immunotherapy

Allergen-specific immunotherapy may be considered for select patients with severe disease with house dust mite, birch, or grass pollen sensitization, and concomitant history of clinical exacerbation after exposure or positive atopy patch test.

Antihistamines³

Oral sedating antihistamines are typically used for soporific effects to facilitate sleep, to prevent an increase of itch intensity at night, and as an adjunctive therapy to topical anti-inflammatory therapy. Studies of oral non-sedating antihistamines have shown variable results in controlling pruritus; however, they may be useful in a small group of patients with associated urticaria. Topical antihistamines are usually not helpful in relieving pruritus and may cause allergic contact dermatitis.

³Various antihistamines are available. Please see the latest MIMS for specific formulations and prescribing information.

Skin Infections⁴  

Clinical infections at treatment sites should be cleared before starting anti-inflammatory agents. Reservoirs of the disease may need to be treated to prevent recurrence (eg nose, groin).  

Bacterial Infections  

Staphylococcus aureus is commonly cultured from eczematous skin and is often the cause of localized infections.  

Short-term topical therapy may be used to treat localized areas. Fusidic acid, Mupirocin, Neomycin, and Retapamulin are treatment options. Retapamulin is recommended for children >9 months. Neomycin may cause allergic contact dermatitis.  

Oral therapy is usually necessary to treat widespread infected lesions. Anti-staphylococcal penicillins (eg Flucloxacillin), macrolides (eg Clarithromycin, Erythromycin), first- and second-generation cephalosporins, and Clindamycin are treatment options. Flucloxacillin is recommended as the first-line therapy for patients with secondary bacterial infections. Alternative treatments to Flucloxacillin include Clarithromycin and Erythromycin. 

Fungal Infections  

Fungal infections may be considered as a possible complication of atopic dermatitis. Antifungal therapy (eg topical Ketoconazole or Ciclopirox olamine, systemic Itraconazole or Fluconazole) may be considered in patients with head and/or neck involvement or with IgE-sensitization to Malassezia spp. Superficial dermatophytosis and Pityrosporum ovale may be treated with systemic or topical antifungals.

Viral Infections  

Patients may develop secondary herpes infections inclusive of eczema herpeticum and Kaposi’s varicelliform eruption and may require systemic Acyclovir or Valaciclovir treatment in a hospital setting. Topical agents such as potassium hydroxide (KOH), Cantharidin, Tretinoin, or Cidofovir, and physical treatments such as cryotherapy and curettage, may be used for eczema molluscatum.  

⁴Various antibiotics, antifungals, and antivirals are available. Please see the latest MIMS for specific formulations and prescribing information.

Other Pharmacotherapeutic Options

Further studies are needed to prove the efficacy of probiotics, topical sodium cromoglycate, vitamin D, Tofacitinib, mast cell stabilizers, and leukotriene antagonists (eg Montelukast) in atopic dermatitis. Vitamin D supplementation and the use of prebiotics or probiotics may reduce symptoms but are not routinely recommended. 

Patient Education

Patient or Caregiver Education  

Discuss the chronic nature of atopic dermatitis, exacerbating factors, and appropriate treatment options with the patient or caregiver. Emphasize that atopic dermatitis tends to decrease with increase in age. Convey that the goal of treatment is control rather than “cure”. Discuss that many factors probably contribute to flare-ups and usually a specific cause cannot be found.  

Educate the patient about proper skin care (eg bathing, hydration, and use of moisturizers). The patient or caregiver should be instructed to apply emollients liberally 3 minutes after taking a bath two to three times daily or frequently as the skin gets dry even in the absence of symptoms. Studies showed that correct and adequate instructions for the use and application of moisturizers when done properly reduce disease severity and the overall topical corticosteroid use. This may improve disease awareness, manage expectations, and enhance treatment adherence.  

Supportive stress-reduction training, including relaxation training and cognitive behavioral therapy, and behavioral therapy to stop habitual scratching, should be discussed with the patient.  

Explain the importance of therapy adherence, appropriate drug therapy, and potential side effects of medications when used over extended periods of time. Apply topical steroids 10 to 15 minutes after the application of emollients.  

Advise patients to keep their fingernails trimmed short and to use cotton gloves at night to limit scratching. 

Lifestyle Modification

Avoidance of Trigger Factors

Identify and Eliminate Trigger Factors  

Identify potential allergens by careful history and selective allergy tests. Skin prick tests and serum tests for allergen-specific IgE are only useful if there is a suspected allergen. Negative results are useful for ruling out suspected allergens. In vitro allergy tests or positive skin prick tests do not always correlate with the clinical symptoms (especially foods) and controlled food challenges, atopy patch tests, or elimination diets may be needed. Limited food allergy testing may be considered in children <5 years with moderate-severe or refractory disease and/or a history of an allergic reaction after a particular food exposure. Most children will outgrow food hypersensitivity within the first few years of life. Patch tests may be done if contact dermatitis is suspected such as palmar or facial dermatitis.

Advise patients to avoid foods identified as allergens in controlled food challenges. Avoidance of aeroallergens (eg house dust mites) may improve symptoms. Advise patients to use dust mite-proof encasings on pillows, mattresses, and box springs, wash bedding weekly in hot water (>58°C), remove bedroom carpeting and curtains, and decrease indoor humidity to levels below 60%. Evidence suggests that allergen-specific immunotherapy may be an option in treating select patients with sensitivity to aeroallergens. 

In most cases, trigger factors cannot be specifically identified, thus advise the patient to apply a holistic approach to avoidance since trigger factors are usually multiple. 

Common trigger factors for atopic dermatitis include wool clothing, pollen, extreme temperature, sweat, products with perfumes or preservatives, foods, cigarette smoke, and animal dander. Psychological factors may also trigger atopic dermatitis. Emotional factors (eg anxiety, stress, and anger) cause disease exacerbation, induce immune activation, and increase pruritus and scratching. Psychological evaluation and counseling should be considered in patients with difficulty with emotional triggers or psychological problems. 

Skin Care

Emphasize the importance of a holistic skincare routine which includes cleansing, moisturizing, treatment, and sun protection. Improvement in symptoms and reduction in side effects of topical therapy such as corticosteroids in atopic dermatitis improve adherence to treatment.  

Appropriate skin care reduces the incidence of flares and increases the time between flares. Hydration of skin with emollients and restoration of skin barrier function are essential to the treatment of atopic dermatitis. Regular skin cleansing with the use of soaps, synthetic detergent (syndet) bars, and topical antiseptics and antibiotics helps reduce abnormal microbial colonization to restore the skin microbiome.

Bathing¹ 

Bathing helps cleanse the skin by removing scales, crusts, bacteria, allergens, and irritants. Soap substitutes with minimal defatting activity, moisturizer-containing, fragrance-free, hypoallergenic, and a neutral to low pH are preferred. 

The ideal hot water temperature for bathing or showering is approximately 38-40°C since a skin temperature of ≥42°C induces an itching response. Once- or twice-daily, short, lukewarm water baths followed by immediate application of moisturizers are recommended for atopic dermatitis patients. 

Advise patients that, if possible, limit soap use to hands, feet, genitalia, and axillae and limit bathing to once daily for 5 to 10 minutes using warm water. Advise them to pat dry after a bath and apply moisturizer or bath oils within 2 to 3 minutes of a bath. 

Studies have shown a decrease in bacterial infection (eg staphylococcal, methicillin-resistant Staphylococcus aureus [MRSA]), disease severity, and flare-ups in patients taking regular bleach baths (1:1200 dilution of 6% hypochlorite bleach; 10-minute soak, three times per week). Bleach baths with intranasal Mupirocin are highly recommended for patients with moderate to severe disease with recurrent secondary bacterial infection. Topical antiseptic agents (eg Sodium hypochlorite 0.005% bath) may be considered in patients with chronic, treatment-resistant disease. 

Salt baths may also be used to help shed dead keratin materials from the skin. Oatmeal products added to baths may be soothing but do not increase water absorption by the skin. Thermal spring water balneotherapy may be considered in patients with mild to moderate disease. Topical medications are best applied after bathing because of greater penetration of hydrated skin. 

¹Various products are available. Please see the latest MIMS for specific formulations and prescribing information.

Moisturizers¹ 

Moisturizers are considered the mainstay of atopic dermatitis treatment as they improve skin barrier function, reduce the incidence of flares, increase the time between flares, and have steroid-sparing effects. 

Atopic Dermatitis_Management 2

Other Therapy

Wet Wrap Therapy  

Wet wrap therapy may be used for chronic and refractory lesions or for moderate to severe weeping lesions. It cools inflamed skin, maintains hydration, and decreases scratching. It can help reduce water loss and disease severity in patients with moderate to severe atopic dermatitis. When combined with topical corticosteroids, it can be effective in treating refractory cases.  

Phototherapy  

Phototherapy is considered in patients with recalcitrant disease or when first-line therapy with topical agents has been unsuccessful.

Atopic Dermatitis_Management 3

Prevention

The identification and elimination of triggering factors are the mainstay for the prevention of flares as well as for the long-term treatment of atopic dermatitis.  

Breastfeeding or feeding with hypoallergenic hydrolyzed formula milk was shown to be beneficial. If the patient with atopic dermatitis is also diagnosed with food allergy, the mother should be advised to eliminate all identified food allergens from her diet.  

Immunization against varicella-zoster virus infection should be encouraged to prevent secondary local or systemic bacterial infection in children with atopic dermatitis. Probiotics may also reduce the incidence or severity of atopic dermatitis, however, more studies are needed to prove this benefit.